Genetic variants of glutathione S-transferase and the risk of acute myeloid leukemia in a Saudi population

Abstract

ObjectiveThis study aims to investigate the genetic association of acute myeloid leukemia and glutathione S-transferase (GST) gene polymorphisms in a Saudi population.Method100 AML cases and 100 healthy controls were recruited from the Riyadh regional hospital. In the GST gene, GSTM1 and GSTT1 variants were genotyped by multiplex PCR, and GSTP1 variants were genotyped by PCR-RFLP analysis. Statistical analysis between AML cases and controls included anthropometric measurements and evaluation of the genotypic and allelic frequencies.ResultThe null genotypes of GSTM1 and GSTT1 showed no association with AML [OR 0.56 (0.26–1.19); p = 0.31 and OR 0.65 (0.37–1.16); p = 0.14]. Similarly, the GSTP1 genotype and allele frequencies did not indicate any association with AML [GG + AG vs. AA: OR 0.75 (0.43–1.31) and p = 0.32; GG vs. AA: OR 1.73 (0.55–5.44) and p = 0.34; G vs. A: OR 0.95 (0.61–1.46) and p = 0.82]. Further, a haplotype analysis between AML cases and controls did not show any positive association (p < 0.05).ConclusionIn conclusion, there was no statistical association of the genotypes and alleles in GSTM1, GSTT1, and GSTP1 with AML. Our results confirm the negative association of the investigated genetic markers with susceptibility to AML. Further association studies would be required in different ethnic populations to facilitate a meta-analysis in the future. Our findings suggest that the GST gene has no role in the pathogenesis of AML in patients from Saudi Arabia.

GSTT1null and rs156697 Polymorphism in GSTO2 Influence the Risk and Therapeutic Outcome of B-Acute Lymphoblastic Leukemia Patients

“…GSTM1 and GSTT1 null are considered loss-of-function mutations as they involve the loss of structural homozygosity and predominantly lead to loss in the corresponding enzyme activity ( 6 ). In the GSTP1 gene, the common A to G transition at 1578 nucleotide position within exon 5 reverts the isoleucine residue (A allele) with valine (G allele) at codon 105 and affects the conjugative ability of reducing glutathione ( 30 ). The presence of the G allele decreases the enzymatic efficiency of GST and in turn decreases the antioxidant capacity and increases the oxidative stress and subsequent cellular damage ( 30 ).…”

“…In the GSTP1 gene, the common A to G transition at 1578 nucleotide position within exon 5 reverts the isoleucine residue (A allele) with valine (G allele) at codon 105 and affects the conjugative ability of reducing glutathione ( 30 ). The presence of the G allele decreases the enzymatic efficiency of GST and in turn decreases the antioxidant capacity and increases the oxidative stress and subsequent cellular damage ( 30 ). This polymorphism results in reduction of the enzyme activity and is associated with the presence of a high level of hydrophobic DNA adducts ( 31 , 32 ).…”

Increased Oxidative Stress in Acute Myeloid Leukemia Patients after Red Blood Cell Transfusion, but Not Platelet Transfusion, Results Mainly from the Oxidative/Nitrative Protein Damage: An Exploratory Study

“…SOD is the most common antioxidant enzyme, while glutathione-S-transferases belong to a super-family of phase II drug-metabolizing enzymes, important in detoxifying xenobiotics and by-products of DNA oxidation. Polymorphisms of GST genes were promising candidate biomarkers for evaluating the AML risk, which may also affect the treatment of leukemia, as GSTs have a role in detoxifying active metabolites of cytotoxic chemotherapeutic agents [ 29 ]. Lack of the significant differences between SOD, GST, and LDH in the AML compared to control groups may be a result of a large dispersion of the results due to individual differences in the studied groups, but our results remain in agreement with previous findings.…”

Screening of V617F mutation in JAK2 gene with acute myeloid leukemia in the Saudi population

“…All recruited samples were collected from Riyadh regional laboratory, Saudi Arabia. Both AML cases and control subjects were recruited based on the inclusion and exclusion criteria, as described in the previous publication (Farasani, 2019). The inclusion criteria of AML subjects were recruited based on the diagnosis of the AML with histopathological and cytogenetic confirmation, and informed consent signed by Saudi adults.…”

“…During diagnosis, AML patients exhibit 50-60% in chromosomal anomalies, and karyotyping plays a significant role in disease-related prognostic factors for care. Despite major advancements in the diagnostic and therapeutic processes, patients with AML have a poor prognosis (Farasani, 2019).…”